Qiu H B, Sun W D, Yang X, Jiang Q Y, Chen S, Lin D G
College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
Res Vet Sci. 2015 Dec;103:143-8. doi: 10.1016/j.rvsc.2015.10.003. Epub 2015 Oct 19.
Breast cancer 1, early onset (BRCA1) is one of the most important genes in human familial breast cancer, which also plays an important role in canine mammary tumors. The objectives of this study were to determine the promoter sequence of canine BRCA1, to investigate its promoter mutation status and to describe BRCA1 expression pattern in canine mammary tumors. The promoter sequence of canine BRCA1 was acquired by aligning human BRCA1 promoter sequence with canine genomic sequence and confirmed by standard promoter activity analysis. Same as human BRCA1 promoter, the CAAT box and G/C box were found in canine BRCA1 promoter. In order to explore the mutation status of the promoter region and to investigate the expression pattern of this gene, 10 normal canine mammary tissues, 15 benign mammary tumors and 15 malignant mammary tumors were used. By sequencing, 46.7% of the malignant mammary tumors were found with a deletion of one cytosine in the promoter region. The mRNA expression of BRCA1 was significantly reduced in benign and malignant mammary tumors (P<0.05), and the protein expression of BRCA1 was significantly reduced in malignant mammary tumors (P<0.05). This study is the first time to determine the canine BRCA1 promoter sequence and to describe the promoter mutation status in canine mammary tumors.
乳腺癌1号基因（BRCA1）是人类家族性乳腺癌中最重要的基因之一，在犬乳腺肿瘤中也发挥着重要作用。本研究的目的是确定犬BRCA1的启动子序列，研究其启动子突变状态，并描述BRCA1在犬乳腺肿瘤中的表达模式。通过将人类BRCA1启动子序列与犬基因组序列比对获得犬BRCA1的启动子序列，并通过标准启动子活性分析进行确认。与人类BRCA1启动子相同，在犬BRCA1启动子中发现了CAAT盒和G/C盒。为了探索启动子区域的突变状态并研究该基因的表达模式，使用了10个正常犬乳腺组织、15个良性乳腺肿瘤和15个恶性乳腺肿瘤。通过测序，发现46.7%的恶性乳腺肿瘤在启动子区域有一个胞嘧啶缺失。BRCA1的mRNA表达在良性和恶性乳腺肿瘤中均显著降低（P<0.05），BRCA1的蛋白表达在恶性乳腺肿瘤中显著降低（P<0.05）。本研究首次确定了犬BRCA1启动子序列并描述了犬乳腺肿瘤中的启动子突变状态。
